OBJECTIVE:Some postmenopausal women use over-the-counter dehydroepiandrosterone because of its purported beneficial effects. Although without major inherent androgenic activity, it is metabolized to potent androgens and estrogens. We investigated the pharmacokinetics of dehydroepiandrosterone and its relevant metabolites after prolonged treatment of postmenopausal women with 25 mg/d of dehydroepiandrosterone. METHODS:Twenty healthy postmenopausal women were randomized to either 25 mg/d of dehydroepiandrosterone or placebo for 6 months. Frequent blood samples were obtained over 24 hours on day 1 and after 3 and 6 months. RESULTS:Mean baseline androgen levels at day 1 and month 3 in the treated group (seven evaluable women) were the following: dehydroepiandrosterone, 1.82 and 3.56 ng/mL; dehydroepiandrosterone sulfate, 0.96 and 3.37 microg/mL; 5-androstene-3beta,17beta-diol, 0.32 and 0.66 ng/mL; androstenedione, 0.50 and 0.86 ng/mL; testosterone, 17.9 and 28.7 ng/dL; dihydrotestosterone, 6.91 and 17.4 ng/dL; and 3alpha-androstanediol glucuronide, 2.66 and 10.7 ng/mL, respectively; these increases were significant. Small changes (-6% to 16%) were observed from month 3 to month 6. Nonsignificant increases were observed in baseline estrone and estradiol levels and in Cmax and AUC0-24h values for the androgens and estrogens from day 1 to months 3 and 6 of treatment. Sex hormone-binding globulin levels were unchanged, but free testosterone increased significantly from day 1 to month 3. Baseline hormone levels did not increase in the placebo group (six evaluable women). Changes in baseline values over time differed significantly between the groups for all hormones except estrone and estradiol. CONCLUSIONS:In postmenopausal women treated orally with a commonly available dose of dehydroepiandrosterone, the daily exposure (AUC) of dehydroepiandrosterone and its principal androgenic metabolites was found to be similar during 6 months of treatment despite increased serum baseline concentrations of these androgens.

OBJECTIVE:To determine the effect of administering 6 months of oral postmenopausal DHEA therapy on serum DHEA, DHEAS, and T levels and on physiologic endpoints including lipoproteins and insulin-like growth factor-I (IGF-I). DESIGN:Randomized, double-blind, parallel trial. SETTING:Academic referral practice. PATIENT(S):Thirteen normal-weight or overweight, healthy, nonsmoking, postmenopausal women. INTERVENTION(S):Administration of oral micronized DHEA (25 mg/d). MAIN OUTCOME MEASURE(S):Monthly fasting 23 hours postdose levels of serum DHEA, DHEAS, T, lipoproteins, IGF-I, IGF binding protein-3 (IGFBP-3), and liver function tests. Morphometric indices by dual-energy x-ray absorptiometry scan (percent body fat; lean body mass), immune indices, and insulin sensitivity. RESULT(S):Levels of DHEA, DHEAS, and T all rose into premenopausal ranges, but after 6 months, levels of DHEA and T did not differ from baseline or placebo. At 3 months, the ratio of IGF-I to IGFBP-3 rose by 36.1% +/- 12.7%, but it fell to placebo values by 6 months. High-density lipoprotein and apolipoprotein A1 levels declined. CONCLUSION(S):Patients appeared to tolerate 6 months of DHEA therapy well. Given the small study size, no statistically significant differences in morphometric indices, immune indices, or insulin-sensitizing properties were observed, but significant attenuation of bioavailability occurred. Supplementation with DHEA increased IGF-I/IGFBP-3 levels at 3 months and decreased high-density lipoprotein and apolipoprotein A1 levels at 6 months.

A procedure utilizing co-chromatography and complementary antiserum comparisons was employed to assess the specificity of a cortisol radioimmunoassay for use in the chronically catheterized fetal sheep preparation. Complementary antiserum comparisons is a technique by which two different cortisol antisera, prepared from conjugates attached at opposite ends of the cortisol molecule, were used to determine cortisol concentrations in the same ovine fetal plasma specimens. Results were not significantly different between the two groups, each measured by a different antiserum. This procedure may be used to assess assay specificity in any species in which steroid radioimmunoassays are being adapted.

This report describes aggregate time trend effects of advancing gestational age on circulating maternal concentrations of progesterone (P), 16α-hydroxyprogesterone, 17α-hydroxyprogesterone (17P), 20α-dihydroprogesterone (20P), Δ5-pregnenolone sulfate, Δ5-pregnenolone (Δ5P), and 17-hydroxyΔ5-pregnenolone (17Δ5P) in a sequential series of 153 blood samples obtained from 19 normal pregnant women ranging from 26-40 weeks gestational age. After logarithmic transformations and curve-fitting procedures, significant differences in slopes were sought and tested by multivariate least squares methods. All steroids, except for 17Δ5P, were markedly elevated above previously reported nonpregnancy concentrations and plotted as positive sloping curves. Log (P) and log (20P) concentration-time curves describe single segment linear curves of similar slope (P > 0.05) and are consistent with the hypothesis that 20P is a metabolite of P, sharing in a relatively stable interconversion with P as the major placental secretory pr...

A massively obese, amenorrheic young woman had elevated levels of plasma androgens which could be reduced either acutely by dexamethasone administration or chronically by weight loss. Normalization of plasma androgen levels in both instances led to resumption of ovulation, suggesting that weight-related hyperandrogenism is a cause of amenorrhea in obesity.

A radioimmunaassay method for the measurement of progesterone (P) in plasma after selective solvent extraction with hexane is described. Utilizing specific antisera against P with minimal or no cross reaction with other steroids, P was measured accurately in a volume of 0.5 ml of plasma. The range of P levels that could be measured per mi of plasma in the assay system described varied from 0.04 to 40 ng/ml. Comparison of the P levels obtained by this rapid assay and by o proven chromatographic system suggests adequate specificity of this quick method.

A relatively simple and rapid radioimmunoassay (RIA) for the measurement of aldosterone in serum and urine has been developed. The method involves extraction of 1 ml of serum or urine (after acid hydrolysis) with dichloromethane, followed by partition chromatography on celite microcolumns prior to RIA. Dextran coated charcoal is used for separation of free from antibody-bound aldosterone. The method is very sensitive, blanks are negligible and recovery is approximately The%. 80 coefficient of variation is 4. 3% (within assay) and 10. 4% (between assay). When known amounts of aldosterone were added to serum and urine pools containing low endogenous levels of this steroid recovery was quantitative. Aldosterone concentrations measured under various physiological conditions were in agreement with published data. Up to 150 samples can be assayed by 1 technician during 5 working days.

Abstract Combining a simple chromatographic system on celite microcolumns with specific antisera as binding reagents, simultaneous radioimmunoassay of pregnenolone (5Δ-P), 17-hydroxypregnenolone (17-5Δ-P), and dehydroepiandrosterone (DHEA) could be performed on the same aliquot of plasma. These steroids have been measured in plasma samples obtained from subjects of both sexes under various conditions. The plasma levels of 5Δ-P, 17-5Δ-P, and DHEA were found to be within the same range when 12 prepubertal boys and 15 men were studied. The mean levels of these steroids were respectively: 1.57, 0.95, and 1.2 ng/ml in prepubertal boys and 0.88, 0.73, and 1.82 in adult men. Six premenopausal women were studied during a complete menstrual cycle. Comparing the levels of 5Δ-P, 17-5Δ-P, and DHEA during the follicular and luteal phases showed no significant difference between these two phases of the cycle. However, plasma 5Δ-P was found to be significantly elevated in the luteal phase when the mean follicular and lu...

Abstract Specific antibodies against diethylstibestrol (DES) were obtained from one ewe immunized against DES-Succinate-human serum albumin conjugate. Using tritiated DES as a tracer, a radioimmunoassay for DES was developed. The senstivity of the standard curve was between 0.25 and 0.5 ng, using a mass of tracer of about 0.5 ng. The antiserum did not cross react with any naturally occurring steroid tested. After oral administration of 10 mgm of DES to a male subject, plasma DES measured after ether extraction reached peak levels of 18.4 and 18.6 ng/ml of plasma 1 and 2 hours later. Plasma DES was still detectable 10 hours after administration. Proof of the validity of this assay for the measurement of DES in cattle would require testing the interference of many plant nonsteroidal estrogen chemically related to DES.